tbuckley/cabot-search huggingface dataset:
Abstract 12022: Predictors of Mortality in Patients With Biopsy-Proven Cardiac AL Amyloidosis
Authors: Efstratios Koutroumpakis, Adam Niku, Christopher K Black, Humaira Sadaf, Juhee Song, Nicolas L Palaskas, Cezar Iliescu, Jean-Bernard Durand, Anita M Deswal, Louis M Buja, Jose Banchs
Journal: Circulation (2022)

Introduction: Cardiac involvement occurs in ~50% of patients with light-chain (AL) amyloidosis and conveys a poor prognosis. This study examined the role of histopathologic and echocardiographic parameters in predicting mortality. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images were processed for longitudinal strain (global [GLS], apical, mid, basal) as well as radial and circumferential strain of the left ventricle (LV), right ventricle (RV) free wall, left atrium (LA), and right atrium, using the Epsilon EchoInsight Software. A detailed histomorphologic characterization of stored endomyocardial biopsy samples was performed by a cardiac pathologist and scored as &lt; or &gt; 5% AL deposits. Results: We identified 43 patients; 44% were women and 63% white. Median age was 65 years (IQR 59-70). Twenty-two (51%) underwent stem cell transplantation (SCT). A total of 29 patients (67%) died during follow up period (median follow up: 4.2 years (95% CI, 2.8-8.6)). Median overall survival (OS) was 18 months (95% CI, 8.1-37). Lower LA GLS and absence of SCT as a time-varying covariate were significantly and independently associated with increased risk of death in the multivariable cox regression analysis (HR 3.8, 95% CI 1.4-10.2 for LA GLS &lt; 13.5 vs &gt;13.5, p=0.008 and 0.20, 0.06-0.65 for SCT vs no SCT, p&lt;0.001, respectively). Higher LV mass and lower RV TAPSE were associated with increased odds of having &gt;5% of interstitial amyloid deposition on biopsy in the multivariable logistic regression analysis (OR 5.5, 95% CI 1.1-26.8 for &gt;195.6g vs ≤195.6g, p=0.036 and 8.1, 1.2-54.3 for RV TAPSE&lt;1.6cm vs ≥1.6cm, p=0.032, respectively). Conclusions: LA GLS &lt; 13.5 was an independent predictor of mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be justified. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. This finding needs to be confirmed by larger studies in the era of contemporary systemic therapies. Although LV mass and RV TAPSE were associated with higher interstitial amyloid deposition, histopathologic parameters did not predict mortality in this cohort.
Abstract 11819: Self-Care Adherence and Related Factors in Koreans With Heart Failure
Authors: Yujin Jeong, Heajin Yu, Boyoung Hwang
Journal: Circulation (2022)

Introduction: Self-care is pivotal in managing heart failure (HF). However, patients’ adherence to self-care and associated factors are not fully understood in Koreans with HF. The aim of this secondary analysis was to assess the level of adherence to self-care and to identify associated factors in patients with HF. Methods: We analyzed baseline data from 122 HF patients (mean age 66.22 [SD 13.58] years; 50.8% female) enrolled in a randomized controlled trial. To determine adherence to self-care behaviors, the proportion of patients answering “completely agree” or “agree” to each item in the European self-care behavior scale (EHFScBS) was calculated. Based on the situation-specific theory of HF self-care, we investigated the effects of person-related factors (i.e., age, sex, socioeconomic status, health literacy, and self-efficacy), problem factors (i.e., multimorbidity, physical functioning, and depression), environmental factor (i.e., social support), and knowledge on adequate self-care (EHFScBS score &amp;ge; 70) using logistic regression analyses. Results: The mean EHFScBS score was 58.29 (SD 19.23), and 34 patients (27.9%) reported adequate self-care. The adherence rate was lowest for fluid restriction (25.4%) and low salt diet (36.1%). Self-care confidence, depressive symptoms, and social support were significantly associated with adequate self-care in univariate analyses (Table 1). After adjusting for other factors, higher levels of self-care confidence (adjusted odds ratio 1.03, p =.004) and lower levels of depressive symptoms (adjusted odds ratio 0.89, p =.03) were significant factors for adequate self-care. Conclusions: Efforts are needed to help patients with HF to engage in self-care practice. Self-care interventions should focus on promoting self-care confidence and reducing depressive symptoms in patients with HF. Routine assessment of self-care confidence and depressive symptoms may help clinicians to identify high-risk patients.
Abstract 12509: Characterization and Risk Factors for Death or Transplant After Stage Ii/glenn Palliation in Infants With Single Ventricle Heart Disease
Authors: Emily M Bucholz, Minmin Lu, Jeffrey Vergales, Michael Bingler, Christina Ronai, Jeffrey B Anderson, Stacey Lihn, Carole Lannon, Katherine E Bates, Lindsey Reynolds, Lynn A Sleeper, David W Brown
Journal: Circulation (2022)

Background: Infants with single ventricle heart disease have a 20% mortality rate during the first year of life with most deaths occurring prior to Stage II/Glenn. Although the time after the Stage II procedure is believed to be a lower risk period, significant morbidity and mortality may occur during this time. Methods: Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation from 2016-2021 and survived to Stage II operation. Multivariable logistic regression and classification and regression tree analysis were performed to identify risk factors for the composite of mortality or transplantation between Stage II surgery and the first birthday. Candidate variables (n=75) included sociodemographic, prenatal, birth, anatomic, stage I intra- and post-operative, interstage course, and Stage II operative characteristics. Results: Of the 1455 patients in the cohort who survived to Stage II, the overall event rate was 7% (76 (5%) died and 34 (2%) were referred for transplant). Overall event rates at 30 and 100 days after Stage 2 were 2% and 5%, respectively ( Figure 1A ). Independent risk factors for mortality and transplantation included shunt type and AV valve repair at Stage I, ECMO and reintubation after Stage I, pre-operative weight and ≥ moderate AV valve regurgitation prior to Stage II, Stage II cross-clamp time, and comprehensive Stage II surgery ( Figure 1B). Patient race/ethnicity and socioeconomic status were not associated with worse outcome. Conclusions: Mortality rates after Stage II surgery to 1 year of age remain high ~5%. Some of the risk factors identified have been shown to also predict interstage mortality, whereas others (reintubation, pre-operative weight, and Stage II characteristics) may be unique to the period after Stage II. Further research is needed to understand whether risk factor modification results in improved transplant-free survival.
Abstract 12174: Inflammation-Dependent Hydroxyeicosatetraenoic Acids Dysregulate Macrophage Resolution Function
Authors: David Meriwether, Jenny S Sauk, Xiaoxiao Yin, Shoreh Noori, Alan M Fogelman, Martin G Martin, Srinivasa T Reddy
Journal: Circulation (2022)

Introduction and Hypothesis: Macrophage efferocytosis is a critical step in the resolution of inflammation. Dysregulated macrophage efferocytosis has been implicated in the pathogenesis of chronic inflammatory disorders including atherosclerosis and IBD. Nonetheless, the nature of possible dysregulating mechanisms remains incompletely understood. We reported that non-enzymatic lipid peroxidation and the mucosal levels of monohydroxylated PUFAs including 12- and 15-hydroxyeicosatetraenoic acid (HETE) correlated with disease in murine models of IBD. HETEs can form enzymatically and non-enzymatically and can signal through the leukotriene (LT) receptor BLT2. LTB4-BLT1/2 signaling can suppress macrophage efferocytosis capacity. We hypothesized that non-enzymatically derived mucosal HETEs correlate with disease in a murine Crohn’s disease (CD) model and in IBD patient biopsies; and that HETEs suppress murine and human macrophage efferocytosis capacity. Methods: We exploited the stereospecificity of enzymatic HETE formation to determine by chiral-LC-MS/MS the levels of non-enzymatically derived HETEs in intestine from a murine myeloid Cox2 knock-out model of Crohn’s disease (CD) and in human IBD patient biopsies. We assessed the effect of racemic HETEs on the efferocytosis capacity of murine BMDMs and human THP1 macrophages for apoptotic MPRO neutrophils. We performed proteomics using accurate mass LC-MS/MS followed by GO enrichment analysis. Results: Non-enzymatically derived mucosal 5-, 12-, and 15HETE were elevated with disease: a) by 3-4 fold in the murine CD model (p&lt;0.01 to p&lt;0.0001); and b) by 2-3 fold in ileal and colonic biopsies from areas of active inflammation in CD and ulcerative colitis patients compared to remission controls (p&lt;0.05). Racemic HETEs suppressed efferocytosis of apoptotic neutrophils by murine (12- and 15-HETE: p&lt;0.0001) and human (12-HETE: p&lt;0.0001) macrophages. Racemic 12-HETE altered the proteome of efferocytic BMDM by inducing 200 proteins while silencing 200 more (&lt;1% FDR), and by suppressing pathways associated with efferocytosis. Conclusion: Inflammation-dependent HETEs may suppress macrophage efferocytosis in chronic inflammatory disorders including IBD and atherosclerosis.
Abstract 12501: Stronger Positive Correlation Between Left Ventricular Mass Index and E/e' in Patients With Diabetes Compared to Non-Diabetic Subjects
Authors: Hiroyuki Miura, Masahiro Koseki, Seiko Ide, Yasuhide Asaumi, Yoshiaki Morita, Yasutoshi Ohta, Tetsuya Fukuda, Katsunao Tanaka, Takeshi Okada, Takashi Omatsu, Yasushi Sakata, Teruo Noguchi
Journal: Circulation (2022)

Introduction: Diabetes mellitus (DM) has been considered as a background of cardiomyopathy. The aim is to characterize the structural and functional features of the heart in diabetic patients by cardiac magnetic resonance imaging (CMR). Methods: This was a multicenter, retrospective, observational study: patients aged 45 years or older who underwent contrast-enhanced CMR were included. Patients with low left ventricular ejection fraction (LVEF) (LVEF&lt;40%), known cardiomyopathy, history of myocardial infarction, or type 1 DM were excluded. Left ventricular mass index (LVMi), LVEF, and extracellular volume (ECV), which may represent myocardial fibrosis, were evaluated by CMR. Left atrial pressure was estimated by echocardiographic indices such as E/e’. Results: We analyzed 322 patients (age (median [interquartile range]) = 64 [53 - 73], DM (n) = 53). After multivariable adjustment, DM was independently associated with greater LVMi (standard regression coefficient (β) = 0.11, p = 0.037) and lower LVEF (β = -0.12, p = 0.036). In DM patients, LVMi and E/e' were positively correlated (correlation coefficient (R) = 0.46, p = 0.001), with a higher correlation coefficient than those in non-DM patients (R = 0.15, p = 0.022). There was a significant interaction between LVMi and DM for increased E/e' (p = 0.020) (Figure A). ECV also correlated with E/e' only in DM patients (DM, R = 0.55, p = 0.011; non-DM, R = 0.14, p = 0.14), with a significant interaction between ECV and DM for increased E/e' (p = 0.037) (Figure B). Conclusions: CMR revealed that diabetic patients without myocardial infarction had increased LVMi with declined LVEF. Both increased LVMi and ECV were also revealed to be associated with higher E/e' especially in diabetic patients.
Abstract 12585: Flexible Modeling of the Association Between Cumulative Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Risk of Hematopoietic Cancer in Children With Congenital Heart Disease
Authors: Mohammad Sazzad Hasan, Aihua Liu, Liming Guo, Michal Abrahamowicz, Jay S Kaufman, Ariane J Marelli
Journal: Circulation (2022)

Background: High-dose ionizing radiation is a well-established risk factor for childhood malignancies, including hematopoietic cancers (HC). However, data on the effect of low-dose ionizing radiation (LDIR) from medical imaging is conflicting and scant, especially in the pediatric population with congenital heart diseases (CHD). This study evaluated the association between cardiac LDIR exposure and hematopoietic cancers among children with CHD. Methods: A nationwide population-based cohort study was conducted using the Canadian Congenital Heart Disease (CanCHD) database. The study population included children born between 1999 and 2017 with at least one CHD diagnosis in their medical records. The cumulative dose of ionizing radiation corresponding to cardiac diagnostic and therapeutic procedures was quantified considering a 6-month exposure lag. The recency-weighted cumulative exposure (WCE) model, a flexible extension of Cox’s proportional hazards model, was used to assess the association. Results: We identified 139,975 children with CHD born between 1999 and 2017 and followed them for 1,388,681 person-years since birth. In this population, 718 hematopoietic cancer cases were observed. Children with HC were exposed to low-dose ionizing radiation earlier in life (median age at first exposure: 6 vs. 10 months; p=0.03) and had more procedures than those without cancer (mean number of procedures: 0.4 vs. 0.2; p&lt;0.001). The cases received higher cumulative LDIR doses than their counterparts (mean dose: 2.3 vs. 1.1 mSv; p&lt;0.001). We observed that cumulative LDIR doses within five years were associated with increased risk of hematopoietic cancer with the maximum association magnitude around 2 years. Conclusion: This is the first large population-based study documenting increased risk of HC associated with increased dose and recency of the LDIR exposure among children with CHD. Along with these findings, future studies focusing on detecting a threshold effect will help physicians decide the exposure point at which increased surveillance on LDIR exposure should be initiated.
Abstract 12290: Effects of Hemodynamic Triggers and Genetic Predisposition on Endocardial Fibroelastosis Recurrence
Authors: Daniel Diaz-Gil, Natalia Silva-Gomez, Sarah U Morton, Jonathan G Seidman, David Zurakowski, Steven Staffa, Breanna L Piekarski, Gerald R Marx, Sitaram Emani, Pedro J Del Nido, Ingeborg Friehs
Journal: Circulation (2022)

Introduction: Endocardial fibroelastosis (EFE) can be the cause of diastolic dysfunction in congenital heart defects. It is derived through endothelial-to-mesenchymal transformation (EndMT), and flow disturbances have been associated with its development. Surgical resection is the only available treatment, but recurrence is often observed. We sought to determine hemodynamic predictors and genetic predisposition of EFE recurrence for preoperative risk stratification. Methods: In 93 patients undergoing LV-EFE resection from 01/2010-03/2021, univariate and multivariable competing risks analysis was applied to determine the effects of hemodynamic parameters on EFE recurrence. In 48 patients with EFE, we classified patient’s rare de novo , damaging missense, and loss of function variants from whole exome sequencing through gene ontology and pathway network enrichments analysis associated with EndMT and/or reduced myocardial contraction or conduction. Results: 51 patients (54.8%) had EFE recurrence with a median time to recurrence of 2.2 years (95% CI 1.3-3.0). We identified mitral valve area (&lt;1 cm 2 ), LV filling pressures (≥9 mmHg), aortic valve (AoV) mean systolic gradient (≥25 mmHg), and AoV diameter (Z-score ≤ -1.6) as predictors of faster time to recurrence (Fig. 1A). In a scoring system, these predictors together achieved an area under the curve of 0.79. Rare variants in the cohort were found in genes enriched for functions related to EndMT and myocardial conduction/contraction, with 75% of patients possessing a variant in such a gene. The combination of both (n=16) was associated with a significantly higher yearly recurrence incidence (p&lt;0.05, Fig. 1B). Conclusions: The degree of hemodynamic disturbances and genetic predisposition predict the time to recurrence in patients after EFE resection. Understanding mechanisms behind EFE progression might provide an opportunity to prevent recurrence and develop new treatment options.
Abstract 11940: Does Mixing Matter? Is This the Final Device Hurdle for Mri Patients?
Authors: Robert W Biederman, Loretta Gevenosky, Mark Doyle
Journal: Circulation (2022)

Introduction: Over the last decade substantial efforts have been aimed at improving acceptability of pacemakers and ICDs in the MRI. Many labs have evaluated the construction, safety, efficacy, reproducibility and more recently, clinical impact value in such legacy devices. In parallel, there has been extensive effort by major vendors to develop safe MRI compatible devices. To date, there remains few reasons for hesitation in universal use of any PM/ICD in the MRI bore. However, mixing vendor leads and generators remains a major hurdle limiting MRI usage. Hypothesis: Mixed leads and generators has no distinct safety signal from common devices; whether CIED or non-CIED. Methods: We undertook a retrospective DB analysis to determine safety signals in those pts possessing mixed vendor leads and devices. Comparisons of impedance, amplitude, threshold and battery voltage and patient safety etc. were performed. Results: Pts from 5/2010 to 5/2022, representing 1739 pts with CIED (81%) and non-CIED (19%) underwent an MRI in a dedicated CMR Lab. The majority of the mixed cohort were obtained from the non-CIED population (&gt;98%), not having need for generator replacement. Accordingly, 11% of these underwent an MRI to include: 73% neurologic, 8% orthopedic and 19% cardiac indications. In comparison of safety signals between standard and mixed lead/generator implants, there were no differences in any implant parameters either pre-MRI study or post-interrogation (p=NS). Similarly, there were no peri-MRI pt events or reported in the 30d and 180d post-MRI scan (p=NS). Importantly, especially for EP considerations, there were no added complications to interrogations. Moreover, utilizing a similar approach to manipulation of MRI parameters for maximum safety intrinsic to dependent/non-dependent PM status was employed regardless of lead/generator configuration yielding no complications. Conclusions: Employing a similar approach to MRI scanning in those pts with mixed vendor lead/generator configurations yielded no difference in a multitude of safety, interrogation, devices and efficacy parameters. This reassurance suggests, despite inherent incompatibility concerns between vendors while in the magnetic field, no such fears are truly warranted.
Abstract 12731: Implementation Barriers of Class 1a Heart Failure Guideline Recommendations in Developing Countries
Authors: Christian R Guilliod, Vanessa Blumer
Journal: Circulation (2022)

Introduction: In April 2022, the American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) released an updated guideline for the management of heart failure (HF). The degree to which these guideline recommendations can be broadly implemented in resource-limited settings, including some developing countries, has not been described. Methods: The 2022 AHA/ACC/HFSA HF guidelines were reviewed and Class 1A recommendations were analyzed for potential implementation barriers in developing countries. For this analysis, Venezuela was used as a case example. Implementation barriers were analyzed on a Likert-type scale from “not a barrier” to “extreme barrier”. Among recommendations with moderate to extreme implementation barriers, potential limiting factors were specified. Results: A total of twenty-two Class 1A HF recommendations were analyzed for potential implementation barriers. Among them, 8 (36%) were classified as “not a barrier”, 3 (14%) as “somewhat of a barrier”, 5 (23%) as “moderate barrier”, and 6 (27%) as “extreme barrier”. Regarding limiting factors, 10 (50%) were related to non-availably of therapeutic drugs/interventions, 4 (20%) involved high incurring costs, and 6 (30%) were related to lack of formal training in HF and/or multidisciplinary specialized care (Figure). Conclusions: There are potential implementation barriers to Class 1A recommendations made in the 2022 AHA/ACC/HFSA HF guidelines in resource limited settings, particularly in certain developing countries where availability and costs of interventions, and lack of formal HF training, represent important limiting factors. Further endeavors should encourage guideline-based recommendations to address resource-limited settings and efforts should be made to maximize implementation around the world.
Abstract 11856: Characterization of Endothelial Adipose Triglyceride Lipase in a Preclinical Model of Heart Failure With Preserved Ejection Fraction
Authors: Max Stahnke, Juliane Schwanbeck, Madeleine Goeritzer, Dagmar Kolb, Gernot F Grabner, Rolf Breinbauer, Rudolf Zechner, Anna Foryst-Ludwig, Ulrich Kintscher
Journal: Circulation (2022)

Background: Metabolic syndrome and endothelial dysfunction are identified as key drivers of Heart Failure with preserved Ejection Fraction. Endothelial cells have an important barrier function including the control of lipid transport from the coronary circulation to the myocardium. In order to determine the role of EC lipid metabolism in HFpEF, we generated mice with an EC-specific deletion of adipose triglyceride lipase and subjected these mice to a hypertensive-obese two-hit HFpEF model. Methods and Results: Cell culture experiments were performed in HUVECS with a pharmacological ATGL inhibitor NG-497. In vitro experiments showed significant reduction of lipolysis by NG-497 and marked endothelial lipid droplet accumulation. Inducible endothelial cell-specific ATGL knockout mice were generated by crossbreeding Atgl fl/fl mice with Cdh5(PAC)-CreERT2 mice. Animals were randomized in a HFpEF or control group. HFpEF mice received a high fat diet and L-NAME for 15 weeks, while animals in the control group were put on a low fat diet and water. To analyse cardiac function, conventional and speckle-tracking echocardiography were performed. After 15 weeks, cre - littermates (wt) with HFpEF developed obesity and hypertension (body weight: wt-Ctrl: 33.8±2.5g vs. wt-HFpEF: 45.1±4.4g, p=0.0001; systolic blood pressure: wt-Ctrl: 99.9±3.7mmHg vs. wt-HFpEF: 135.5±5.6mmHg, p=0.0001), which did not significantly differ in ecATGL-KO mice. In parallel, wt-HFpEF mice developed echocardiographic signs of HFpEF including diastolic dysfunction: E/é: (wt-Ctrl: -22.1±1.4 vs. wt-HFpEF: -45.5±3.8; p&lt;0.0001), IVRT: (wt-Ctrl: 17.8±0.7ms vs. wt-HFpEF: 19.5±0.8ms; p= p&lt;0.0001), and an impaired global longitudinal strain (GLS) (wt-Ctrl: -20.7±1.1% vs. wt-HFpEF 12.9±0.7%; p&lt;0.0001). Parameters of diastolic dysfunction were significantly improved in ecATGLKO mice after 15weeks of HFD/ L-NAME: E/é:-29.3±2.8; p&lt;0.0001 vs. wt-HFpEF; IVRT: 18.3±0.5; p&lt;0.05 vs. wt-HFpEF; GLS: -19.1±1.7; p&lt;0.0001 vs. wt-HFpEF). Conclusion: This study demonstrates that loss of ATGL in ECs may protect from HFpEF. We hypothesize that lipid droplet accumulation in coronary ATGL-deficient ECs may save the myocardium from lipid overload and lipotoxicity, as shown in Cre- HFpEF mice.